Immunology. Richard Coico
which are brought into proximity by the three‐dimensional folding of the protein. B‐cell membrane immunoglobulins and antibody are capable of recognizing polysaccharides and lipids.
5 T cells recognize internal amino acid sequences of proteins in the context of MHC class I or class II molecules. Peptide fragments of protein antigens generated by antigen processing may associate with MHC molecules and be presented to T cells.
6 Immunological cross‐reactivity denotes a situation in which two or more substances, which may have various degrees of dissimilarity, share epitopes and would, therefore, react with the immune components induced against any one of these substances. Thus a toxoid, which is a modified form of toxin, may have one or more epitopes in common with the toxin. Immunization with the toxoid leads to an immune response capable of reacting not only with the toxoid but also with the native toxin.
7 Adjuvants are substances that can accelerate, prolong, and enhance the quality of specific immune responses. When administered with antigens, adjuvants facilitate immune responses that are specific for the antigen (not for adjuvant itself) since the adjuvant nonspecifically amplifies the response. The principal mechanisms include increased antigen presentation by APCs (especially dendritic cells), induction of co‐stimulatory molecules, and induction of local inflammatory cytokine responses.[xnl][xsb]
REFERENCES AND BIBLIOGRAPHY
1 Ahmed SS, Plotkin SA, Black S, Coffman RL. (2011) Assessing the safety of adjuvanted vaccines. Sci Transl Med 3(93): 9.
2 Atassi MZ. (1977) Immunochemistry of Proteins, vols 1 and 2. New York: Plenum.
3 Benjamin DC, Berzofsky JA, East IJ, Gurd FRN, Hannum C, Leach SJ, Margoliash E, Michael JG, Miller A, Prager EM, Reichlin M, Sercarz EE, Smith‐Gill SJ, Todd PE, Wilson AC. (1984) The antigenic structure of proteins: a reappraisal. Annu Rev Immunol 2: 67.
4 Berzofsky JA, Cease KB, Cornette JL, Spouge JL, Margalit H, Berkower IJ, Good FM, Miller LH, DeLisi C. (1987) Protein antigenic structures recognized by T cells: potential applications to vaccine design. Immunol Rev 98: 9.
5 Carroll EC, Jin L, Munoz‐Wolf N, Oleszycka E, Moran HBT, Mansouri S, McEntee CP, Lambe E, Agger EM, Anderson P, Cunningham C, Herzog P, Fitzgerald KA, Bowie AG, Lavelle EC (2016) The vaccine adjuvant chitosan promotes cellular immunity via DNA sensor cGAS‐STING‐dependent induction of type I interferons. Immunity 15:597.
6 Christian RR, Mandl W, Black S, De Gregorio E. (2011) Vaccines for the twenty‐first century society. Nat Rev Immunol 11: 865.
7 Davis DR, Cohen GH. (1996) Interactions of protein antigens with antibodies. Proc Natl Acad Sci USA 93: 7.
8 Davis MM, Boniface JJ, Reich Z, Lyons D, Hampl J, Arden B, Chien Y. (1998) Ligand recognition by αβ T cell receptors. Annu Rev Immunol 16: 523.
9 Freund J, Calals J, Hosmer EP. (1937) Sensitization and antibody formation after injection of tubercle bacilli and paraffin oil. Proc Soc Exp Biol Med 37: 509.
10 Global Advisory Committee on Vaccine Safety, June 2012. (2012) Wkly Epidemiol Rec 87(30): 281.
11 Mastelic B, Ahmed S, Egan WM, Del Giudice G, Golding H, Gust I, Neels P, Reed SG, Sheets RL, Siegrist CA, Lambert PH. (2010) Mode of action of adjuvants: implications for vaccine safety and design. Biologicals 38(5): 594.
12 Novotny J, Handschumacher H, Bruccoleri RE. (1987) Protein antigenicity: a static surface property. Immunol Today 8: 26.
13 Rothbard JB, Gefter ML. (1991) Interactions between immunogenic peptides and MHC proteins. Annu Rev Immunol 9: 527.
14 Watts C. (1997) Capture and processing of exogenous antigens for presentation on MHC molecules. Annu Rev Immunol 15: 821.
REVIEW QUESTIONS
For each question, choose the ONE BEST answer or completion.
1 A large glycoprotein has been enzymatically digested in the laboratory to yield a mixture of glycopeptides ranging in size from 4 to 6 amino acids in length. Which of the following would be expected if the peptide mixture were administered to an experimental animal together with an adjuvant such as complete Freund’s adjuvant?Peptide‐specific antibodies would be generated using the peptide mixture alone.Carbohydrate‐specific antibodies would be generated only if an adjuvant were administered with the peptide mixture.peptide‐specific antibodies would be generated only if they were injected with a separate uncoupled protein carrier.Peptide‐specific and carbohydrate‐specific antibody and T‐cell responses would be generated using the peptide mixture alone.There would be neither a humoral nor cell‐mediated immune response to the peptides in the mixture.
2 The protection against smallpox virus infection afforded by prior infection with cowpox virus represents:antigenic specificityantigenic cross‐reactivityenhanced viral uptake by macrophagesinnate immunitypassive protection
3 Converting a toxin to a toxoid:makes the toxin more immunogenicreduces the pharmacological activity of the toxinenhances binding with antitoxininduces only innate immunityincreases phagocytosis
4 Haptens:require carrier molecules to be immunogenicreact with specific antibodies when homologous carriers are not employedinteract with specific antibody even if the hapten is monovalentcannot stimulate secondary antibody responses without carriersall of the above
5 An adjuvant is a substance that:increases the size of the immunogenenhances the immunogenicity of haptensincreases the chemical complexity of the immunogenenhances the immune response to the immunogenenhances immunological cross‐reactivity
6 A polyclonal antibody made against a large protein antigen reacts with it even when it is denatured by disrupting all disulfide bonds. A monoclonal antibody against the antigen fails to react with it when it is similarly denatured. The most likely explanation can be stated as follows.The polyclonal antibody contains antibodies specific for several nonconformational epitopes expressed by the antigen.The monoclonal antibody recognizes both conformational and nonconformational epitopes.The monoclonal antibody is specific for disulfide bonds.The polyclonal antibody has a higher affinity for the antigen.
ANSWERS TO REVIEW QUESTIONS
1 E. Peptides ranging from 4 to 6 amino acids in length are low molecular weight molecules that are unable to generate antibody responses or T‐cell responses due to their small size. If these peptides were coupled or bound to a protein carrier, they could be immunogenic. T cells do not generate T‐cell responses to carbohydrates; therefore D is incorrect.
2 B. The protection against smallpox provided by prior infection with cowpox is an example of antigenic cross‐reactivity. Immunization with cowpox leads to the production of antibodies capable of reacting with smallpox because the two viruses share several identical, or structurally similar, determinants.
3 B. Conversion of a toxin to a toxoid is performed in order to reduce the pharmacological activity of the toxin so that sufficient toxoid can be injected to induce an immune response.
4 E. Haptens are substances, usually of low molecular weight and univalent, that by themselves cannot induce immune responses (primary or secondary), but can do so if conjugated to high molecular weight carriers. The haptens can and do interact with the induced antibodies without it being necessary that they be conjugated to the carrier.
5 D. An immunological adjuvant is a substance that, when mixed with an immunogen, enhances the immune response against that immunogen by mechanisms that depend upon the specific adjuvant used (e.g., enhanced antigen presentation, delayed release of antigen, etc.). It does not increase its size or chemical complexity. In addition, it does not enhance the immune response against a hapten, which requires its conjugation to an immunogenic carrier to induce a response against the hapten. The adjuvant has no relevance to possible toxicity of an immunogen.
6 A. Polyclonal antibodies are a mixture of antibodies produced by multiple B‐cell clones with B‐cell receptors that react with